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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the diagnostic utility of urinary transferrin (Tf) in patients with diabetic nephropathy by comparing the diagnostic findings with those of clinical stage and renal biopsy specimens. According to the rate of urinary albumin excretion, a total of 60 patients with non-insulin-dependent diabetes mellitus were separated into normoalbuminuria (< 28.8 mg/day), microalbuminuria (28.8 approximately 288 mg/day), and overt proteinuria (> 288 mg/day). They were also divided into 5 groups, D0, DI, DII, DIII and DIV according to the severity of glomerular diffuse lesions using Gellman's criteria. Thirty-eight non-diabetic volunteers were used as controls. Using 24-hour urine specimens, Tf was measured by latex-immuno-turbidimetry. Urinary concentrations of albumin, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) were also evaluated. Urinary Tf was significantly increased in the diabetic patients relative to the non-diabetic controls. The incidence of microtransferrinuria (440 approximately 4,400 micrograms/day) was 33.3% in normoalbuminuria, 63.2% in microalbuminuria, and 18.2% in overt proteinuria. The incidence of overt transferrinuria (> 4,400 micrograms/day) was 0%, 36.8% and 81.8%, respectively. Among the diabetic patients, urinary Tf showed a significant increase with respect to the progress of glomerular diffuse lesions. The glomerular diffuse lesions of 10 normoalbuminuric cases with microtransferrinuria were graded as DI in 8 cases, DII in 1 case, and DIII in 1 case. There was a significant correlation between the urinary excretion of Tf and that of albumin, alpha 1-microglobulin or NAG. The findings indicate that urinary Tf may be useful in detecting diabetic nephropathy at an early stage.
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PMID:Diagnostic significance of urinary transferrin in diabetic nephropathy. 858 2

While it is generally accepted that T cells are critical for the development of diabetes in the non-obese diabetic (NOD) mouse, the precise functions of the CD4+ and CD8+ subsets remain ill-defined. Transfer experiments have provided evidence that CD4+ cells are the disease initiators, provoking massive mononuclear leukocyte infiltration into the pancreatic islets, while CD8+ cells play an effector role, responsible for the final destruction of islet beta cells. It was surprising, then, to find that NOD mice carrying a null mutation at the beta 2-microglobulin (beta 2-mu) locus, and thereby lacking major histocompatibility complex class I molecules and CD8+ T cells, developed neither insulitis nor diabetes. Here, we argue that the absence of insulitis in these animals results from their lack of CD8+ cells because islet infiltration is also absent when NOD mice are treated with an anti-CD8 monoclonal antibody (mAb) at a young age. Interestingly, the anti-CD8 effect is only observed when the mAb is injected during a discrete age window--2 to 5 weeks after birth. Transfer experiments indicate that the lack of CD8+ cells during this period somehow alters the phenotype of CD4+ cells, preventing them from expressing their insulitis potential. This is not because they are generally immuno-incompetent nor because they are generally more prone to differentiating into cells with Th2 characteristics. Given that neither the beta 2-mu mutation nor anti-CD8 treatment affect insulitis in a T cell receptor transgenic (tg) mouse strain with a CD4+ T cell repertoire highly skewed for an anti-islet cell reactivity, the most straight-forward interpretation of these observations is that CD8+ cells are required for effective priming and expansion of autoreactive CD4+ cells.
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PMID:The role of CD8+ T cells in the initiation of insulin-dependent diabetes mellitus. 876 18

It has recently been shown that beta 2-microglobulin isolated from amyloid deposits in dialysis patients is modified by advanced glycation (AGE). In this context it appeared of interest to examine in a cross-sectional multicentre study whether dialysis-related amyloidosis, as evaluated by X-ray assessment of cysts in the metacarpal bones, was different in diabetic patients on maintenance haemodialysis for more than 5 years time compared with matched non-diabetic controls. We evaluated the hand skeleton of 75 diabetic patients (9 type I, 66 type II; 35 male, 40 female; median age 64 years, range 31-86; median duration of dialysis 7 years, range 5-17). They were compared with 150 patients without diabetes mellitus who were matched for age, gender and duration of dialysis. Hand X-rays were centrally evaluated by one radiologist unaware of the underlying clinical diagnosis. The overall frequency of amyloid cysts was 9/75 (12%) in diabetic patients (95% confidence interval 4.6-19.3%) and 28/150 (19%) in matched controls (95% confidence interval 12.4-24.9%). The results indicate that diabetes mellitus does not confer an increased risk of dialysis-related amyloid cysts. The results are of interest with respect to the mechanism of amyloid formation.
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PMID:Prevalence of dialysis-related amyloidosis in diabetic patients. Diabetes Amyloid Study Group. 891 14

Erythritol (20 g in solution) was administered orally in a single-dose to 5 patients with diabetes. Serum erythritol levels reached a peak 1 hr after administration and then declined rapidly. Total urinary excretion was 82.0 +/- 3.7% within 24 hr and 88.5 +/- 3.3% within 72 hr. Serum glucose and insulin levels remained unchanged until a meal was taken (3 hr after erythritol administration) and then increased. Free fatty acids and 3-hydroxybutyric acid levels increased after erythritol administration but dropped after ingestion of food. In a separate clinical trial, erythritol (20 g) was administered orally daily for 14 days to 11 patients with diabetes. Mean serum glucose and hemoglobin A1c levels decreased over the time period. Indices of renal function-blood urea nitrogen, creatinine, and beta 2-microglobulin-did not change significantly. The single dose study suggests that erythritol exerts no significant effects on the metabolism of diabetic patients. Two-week daily administration of erythritol had no adverse effect on blood glucose control.
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PMID:Effects of oral administration of erythritol on patients with diabetes. 893 47

The 10-year follow-up of the Munich General Practitioner Project was designed as a long-term prospective study to evaluate factors predicting macrovascular and overall mortality in a random cohort of non-insulin-dependent diabetic (NIDDM) patients. Of the original 290 patients (103 males, 187 females, median age 65 years) 92.5% could be assessed, 103 subjects had died, 58 from macrovascular causes. In an univariate analysis of baseline data, deceased patients, and especially those who died from macrovascular causes had significantly higher fasting blood glucose, HbA1c, von Willebrand-factor protein, urine albumin excretion, and serum beta 2-microglobulin, were significantly older, exhibited significantly more ischaemic heart disease (abnormal ECG Minnesota codes), carotid artery and peripheral vascular disease (both determined by ultrasound-Doppler), and had significantly inferior knowledge about diabetes and its treatment. No significant differences were seen for gender, blood pressure, smoking, total cholesterol, triglycerides, HDL-cholesterol, or the use of antidiabetic, antihypertensive or coronary drugs. In a multiple logistic regression analysis, the risk factors for macrovascular death were age, HbA1c and von Willebrand-factor protein. When baseline macrovascular disease was taken into account, carotid artery disease was also a determinant. The main variables from the metabolic syndrome (blood pressure, dyslipidaemia, body mass index) did not enter a multiple logistic regression analysis. The data suggest that age and haemoglobin A1c are major determinants, and that in addition von Willebrand-factor associated endothelial damage is a risk factor for macrovascular mortality in NIDDM patients.
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PMID:Predictors of 10-year macrovascular and overall mortality in patients with NIDDM: the Munich General Practitioner Project. 896 Aug 40

Urinary growth hormone (uGH) excretion was evaluated in 96 type-1 insulin-dependent diabetic patients and 37 age-matched healthy subjects. The growth hormone concentration was measured by a solid-phase immunoradiometric assay on 3 consecutive overnight urine collections. uGH excretion was comparable between diabetic patients and healthy subjects: 10.9 (0.1-34.8) vs. 9.1 (2.6-34.5) pg/min. In both groups uGH excretion was lower in prepubertal than in pubescent or pubertal individuals (diabetic patients, H = 29.7, p = 0.001; healthy subjects, H = 10.4, p = 0.006). In diabetic patients uGH excretion was related to beta 2-microglobulin excretion (r = 0.308; p = 0.005) and to urinary albumin excretion (r = 0.230; p = 0.02) but it was independent of HbA1c and overnight glycemic values. The coefficient of variation of uGH excretion was higher in diabetic patients with respect to healthy subjects: 50 (3-141) vs. 28(3-100)% (p = 0.002). Among diabetic patients it was greater in prepubertal than in pubescent or pubertal patients (H = 13.7; p = 0.002); in contrast, it was independent of pubertal stage in healthy individuals (H = 2.4; NS). The coefficient of variation of uGH was not related to HbA1c, the duration of diabetes, the coefficient of variation of urinary albumin excretion and the coefficient of variation of beta 2-microglobulin excretion. In conclusion uGH excretion is comparable among diabetic patients and healthy subjects, but its day-to-day fluctuation is greater in the former than in the latter group. Renal function but not metabolic control can influence uGH excretion. The day-to-day fluctuation in uGH excretion is independent of metabolic control and renal function.
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PMID:Urinary growth hormone excretion in children and adolescents with insulin-dependent diabetes mellitus. 898 38

Advanced glycation end products (AGE) are formed in long-lived matrix proteins by a nonenzymatic reaction with sugar. The presence of AGE in beta 2-microglobulin-amyloid fibrils of dialysis-related amyloidosis, one of the characteristic features of which is an accelerated bone resorption around amyloid deposits, was recently demonstrated. This suggested a potential link of AGE in bone resorption and initiated this investigation of whether AGE enhance bone resorption. When mouse unfractionated bone cells containing osteoclasts were cultured on dentin slices, both AGE-modified beta 2-microglobulin and BSA increased the number of resorption pits formed by osteoclasts, whereas their normal counterparts of those modified with the early glycation products did not. AGE proteins, however, did not increase the number of newly formed osteoclasts, even in the coculture of mouse bone marrow cells with osteoblastic cells isolated from mouse calvaria. Enhanced bone resorption was also observed when unfractionated bone cells were cultured on AGE-modified dentin slices. AGE-enhanced bone resorption was effectively inhibited by calcitonin and ipriflavone, both of which are inhibitors of bone resorption. AGE-enhanced bone resorption was further supported by in vivo evidence that rat bone particles-upon incubation with glucose for 60 days (AGE-bone particles)-when implanted subcutaneously in rats, were resorbed to a much greater extent than control bone particles upon parallel incubation without glucose. These findings suggest that AGE enhance osteoclast-induced bone resorption. Although the mechanism remains unknown, AGE are unlikely to promote differentiation of osteoclast progenitors into osteoclasts, suggesting that AGE activate osteoclasts or alter microenvironments favorable for bone resorption by osteoclasts. The modification of bone matrices with AGE might play a role in the remodeling of senescent bone matrix tissues, further implicating a pathological significance of AGE in dialysis-related amyloidosis or osteoporosis associated with diabetes and aging.
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PMID:Advanced glycation end products enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted subcutaneously with devitalized bone particles. 904 45

More negatively-charged proteins are harder to pass through the glomerular charge barrier (GCB) and to be reabsorbed by renal tubules. Although the glycation of albumin increases its negative charge compared to non-glycated albumin, the glycation of transferrin does not change its charge. This difference enabled us to examine the charge-dependent renal function in diabetic proteinuria. The percentage of urinary glycated transferrin (serum %G-transferrin) positively correlated with serum fructosamine concentrations and the percentage of serum glycated albumin (serum %G-albumin) in all subjects. Urinary concentrations of transferrin and beta 2-microglobulin strongly correlated in diabetic patients with microproteinuria, while no significant correlation was observed in subjects with diabetic macroproteinuria or non-diabetic proteinuria. Urine/serum (U/S) ratio of %G-albumin in the patients with diabetic proteinuria was significantly lower than that in subjects with non-diabetic proteinuria, while no difference of the U/S ratio of %G-transferrin was observed between any groups. Furthermore, U-%G-transferrin/U-%G-albumin ratio was highest in the diabetic patients with microproteinuria. These results lead to the conclusion that the initial damage in diabetic kidney causing microproteinuria starts with the dysfunction of charge-dependent tubular reabsorption prior to a loss of GCB.
Diabetes Res Clin Pract 1997 Apr
PMID:Damage of charge-dependent renal tubular reabsorption causes diabetic microproteinuria. 918 9

Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic NE responsiveness in IDDM. On separate days, NE or placebo was infused at individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg), with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I-iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta 2-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in the other groups (P < 0.05). An NE dose-dependent fall in effective renal plasma flow and rise in filtration fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did not change significantly. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular protein leakage, and it is plausible that intraglomerular NE effects contribute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a specific NE response or a general effect of vasopressor stimuli to promote glomerular protein leakage in patients with a preexistent defect in glomerular permselectivity.
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PMID:Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus. 955 67

Renal dipeptidase (EC 3.4.13.19) activity in serum and urine from healthy volunteers (n = 20), patients with diabetes (n = 18) and patients with chronic renal failure (n = 5) was measured using glycyl-D-alanine as substrate. The assay was highly specific for the enzyme and was not affected by the various aminopeptidases present in serum and urine. No difference in serum renal dipeptidase activity was observed between the groups. The enzyme activity (U/L) in urine was higher than that in serum, irrespective of the group, suggesting the urine concentration was not affected by the serum concentration. The mean renal dipeptidase activities in urine were 2.56, 2.46 and 0.78 U/mol creatinine for healthy subjects, patients with diabetes and patients with chronic renal failure, respectively. The renal dipeptidase activity was significantly lower in the chronic renal failure group. The urinary excretion of dipeptidase (U/mmol creatinine) showed significant inverse correlations with that of beta 2-microglobulin, albumin and alpha 1-microglobulin, and with serum concentrations of creatinine, beta 2-microglobulin and alpha 1-microglobulin. We suggest that urine dipeptidase may be a useful marker of renal diseases.
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PMID:Behaviour of urinary dipeptidase in patients with chronic renal failure. 1037 Jul 41


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